Oxidative stress in obstructive sleep apnea and intermittent hypoxia--revisited--the bad ugly and good: implications to the heart and brain

Sleep Med Rev. 2015 Apr;20:27-45. doi: 10.1016/j.smrv.2014.07.003. Epub 2014 Jul 24.


Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), is linked with increased reactive oxygen species/reactive nitrogen species (ROS/RNS) and oxidative stress, which adversely affect the associated cardio-/cerebro-vascular disease in OSA. Yet, animal and a small number of human studies support activation of cardio-/cerebro-protective mechanisms as well. ROS/RNS are intricate and multifaceted molecules with multiple functions. At low-moderate concentrations ROS/RNS are considered "good", by regulating vital cellular functions. At higher levels, they are considered "bad" by promoting oxidative stress and damaging vital macromolecules through ischemia and reperfusion (I/R) injury. Subsequently, ROS/RNS can get "ugly" by eliciting sterile inflammation and a multitude of deadly pathologies. What makes ROS/RNS good, bad, or ugly? A dynamic interplay between a large number of factors determines the outcomes. These include the types of ROS/RNS produced, their quantity, duration, frequency, intracellular localization, micro-environmental antioxidants, as well as the genetic make-up and life style related variables. This review presents the currently available data on redox biology in physiological/pathophysiological conditions and in OSA/IH, in order to better understand the apparently contradictory findings on damage vs. repair. These findings are discussed within the context of the prevailing views on I/R associated ROS/RNS, and their potential implications to OSA.

Keywords: Acute myocardial infarction; Anti-oxidants; Coronary collaterals; Endothelial progenitor cells; Ischemia/reperfusion; Ischemic preconditioning; Obstructive sleep apnea; Oxidative stress; ROS/RNS; Stroke.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Brain / metabolism
  • Brain / physiopathology*
  • Heart / physiopathology*
  • Humans
  • Hypoxia / complications
  • Hypoxia / etiology*
  • Hypoxia / metabolism
  • Hypoxia / physiopathology
  • Hypoxia, Brain / etiology
  • Hypoxia, Brain / metabolism
  • Hypoxia, Brain / physiopathology
  • Myocardium / metabolism
  • Oxidative Stress / physiology*
  • Reactive Nitrogen Species / metabolism
  • Reactive Oxygen Species / metabolism
  • Sleep Apnea, Obstructive / complications
  • Sleep Apnea, Obstructive / physiopathology*


  • Reactive Nitrogen Species
  • Reactive Oxygen Species